Asthma is a chronic inflammatory disease of the airways that is caused by a complex interaction between genetic and environmental factors. In the US, more than 11 million individuals reported having at least one attack of asthma in 2002, and the number of people with asthma is expected rise to 29 million by 2020. Given the significant mortality, morbidity and economic impact of asthma, it is important to improve treatment of the disease and to develop new strategies and drugs for intervention. Most of the drugs used to control asthma symptoms fall into 3 pharmacological classes: inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRA) and long-acting beta adrenergic receptor agonists (LABA). Clinical trials have established the efficacy and safety of these drugs alone or in combination to treat asthma. However, marked inter-patient variability in response to each of the drugs limit their safety, efficacy and cost-effectiveness. Recent studies suggest that up to 80% of the inter-patient variability in response to asthma drugs is due to genetic variation. The American Lung Association Asthma Clinical Research Centers are performing a clinical trial entitled: LeukotrieneModifier or Corticosteroids (LOCS) trial. Patients 6 years or older with asthma who are stable on inhaled fluticasone (FP) monotherapy for 4 to 6 weeks, will be randomly assigned to continue taking inhaled FP, 100 ug twice a day, OR montelukast, 10 mg at bedtime, OR inhaled salmeterol, 50 ug twice a day, for 16 weeks. 165 patients will participate in each treatment arm (495 total). The LOCS trial was designed to determine if montelukast monotherapy and salmeterol monotherapy can be substituted for inhaled FP without loss of asthma control. The primary outcome is asthma control as determined by the rate of treatment failures with montelukast monotherapy and salmeterol monotherapy compared to inhaled FP. Secondary outcomes include pulmonary function, asthma symptoms including medication use, patient related measures, markers of inflammation and in 200 patients, airway responsiveness to methacholine. The goals of the present ancillary pharmacogenetic study are to identify SNPs in one or multiple genes that predict which patients can be treated with either montelukast or salmeterol monotherapy without loss of control conferred by inhaled FP. The results of this pharmacogenetic study may facilitate the optimal selection of monotherapy in asthma.